Poor differentiation and microvascular invasion (MVI) are crucial prognostic indicators for hepatocellular carcinoma (HCC), but evaluating them before surgery is still difficult. Our goal was to develop a reproducible framework for ultrasound localization microscopy (ULM) using a clinical ultrasound system and assess its effectiveness in predicting tumor differentiation and MVI.

Participants were prospectively enrolled and underwent contrast-enhanced ultrasound and ULM imaging. We first compared frame selection strategies by calculating coefficients of variation (COVs) of ULM parameters derived from motion-variance curve (MVC) alone versus MVC combined with time-intensity curve (TIC). ULM resolution and parameter stability were then assessed across low (0-399), medium (400-699), and high (700-1000) frame counts. Regions of interest (ROIs) were manually drawn on grayscale ultrasound and mapped to ULM images. Inter-operator agreement was evaluated using intraclass correlation coefficients (ICCs). Participants were grouped by pathological differentiation and MVI status. The predictive performance of ULM parameters was assessed with multivariable logistic regression.

Sixty-one HCC participants were enrolled (11 poorly differentiated, 50 well differentiated; 30 MVI-positive, 31 MVI-negative). The MVC+TIC strategy yielded significantly lower COVs, indicating higher repeatability of ULM parameters. Medium frame counts (400-699) provided high resolution (minimum vessel diameter 91.3 ± 22.7 μm) and stable parameters (COV < 20%), and were therefore selected for ULM reconstruction. All ULM parameters showed high inter-operator agreement (ICC 0.876-0.988). Based on the established ULM framework, higher intratumoral mean curvature was independently associated with poor differentiation [area under the curve (AUC) 0.91], and higher peritumoral mean curvature independently predicted MVI status (AUC 0.78).

The reproducible ULM framework enables stable, high-resolution microvascular imaging of HCC. ULM-derived parameters hold potential as novel biomarkers for predicting differentiation grade and MVI status of HCC.

Solitary fibrous tumours (SFT) of the central nervous system (CNS) are rare mesenchymal neoplasms. Challenges arise at the time of diagnosis due to their overlapping clinical, radiological, and histopathological features with other spindle cell tumours. We present four cases of SFTs arising at different anatomical locations across the CNS. The patients presented with varied clinical symptoms and radiological findings, leading to an initial diagnosis of other mimickers, such as fibrous meningioma, neurofibroma, and other spindle cell tumours. Histopathological examination revealed tumours composed of spindle cells and branching, staghorn-like vasculature. Immunohistochemical evaluation with STAT6 was performed in all the cases to distinguish SFT from its histological mimickers. It demonstrated diffuse nuclear staining of tumour cells in all four cases. Based on the histology, mitotic activity, and necrosis, the tumours were classified as CNS WHO Grades 1, 2, and 3. These cases highlight the varied clinical and radiological presentations of CNS SFTs. They also emphasise the importance of careful histopathological assessment with appropriate immunohistochemical workup for accurate diagnosis. Awareness of this entity and its mimickers is essential to avoid misdiagnosis and ensure appropriate patient management.

Squamous cell carcinomas of the head and neck (SCCHN) belongs to a biologically aggressive group of malignancies. The salvage options, after failure of the platinum-based therapy and immune checkpoint inhibitors (ICIs), are usually very limited. The regimen comprising oral methotrexate, erlotinib, and celecoxib (OMCT) has been explored as a well-tolerated, low-dose management option. We present through the case series the clinical outcomes of patients who had recurrent, refractory, or locally advanced SCCHN treated with OMCT in combination with low-dose nivolumab for translatable evidence.

Desmoid-type fibromatosis of the breast is an uncommon, low-grade mesenchymal neoplasm with benign histologic features, characterized by locally aggressive growth and a notable tendency for local recurrence. Clinical management is challenging owing to frequent positive surgical margins, a propensity for recurrence, and the absence of standardized treatment guidelines. We report the case of a 34-year-old woman who underwent mastectomy for recurrent breast desmoid-type fibromatosis, in whom a heterozygous germline MUTYH (MutY DNA glycosylase) variant was identified through hereditary cancer panel testing. This case highlights the potential value of comprehensive pathologic assessment and selective germline genetic testing in patients with recurrent breast fibromatosis, which may offer further insight into tumor biology and inform individualized management strategies.

Surgery remains the cornerstone of prostate cancer treatment, demanding accurate tumor delineation and margin assessment. The hybrid molecule PSMA-914, which combines positron emission tomography (PET) and near-infrared fluorescence (NIRF) detection capabilities, was developed to improve preoperative imaging and intraoperative guidance during prostate cancer surgery.

In this first-in-human series, prostate cancer patients underwent preoperative PET/CT imaging with ⁶⁸Ga-labeled PSMA-914 (n = 10), followed by fluorescence-guided surgery after intraoperative PSMA-914 administration (n = 7, doses ranging from 200 -1500 µg/patient). The optimal dose for effective tumor visualization was retrospectively evaluated, and both preoperative and postoperative imaging results were correlated with histopathological findings.

Preoperative PET/CT with [⁶⁸Ga]Ga-PSMA-914 showed high tracer uptake in primary tumors and metastases, facilitating accurate tumor localization. Intraoperatively, PSMA-914 at doses exceeding 1000 µg/patient provided a clear fluorescence signal, allowing for precise tumor and lymph node delineation. This approach significantly aided surgical resection by providing real-time guidance to differentiate malignant tissue from healthy tissue without altering the standard surgical workflow. Histopathological analysis confirmed the accuracy of [⁶⁸Ga]Ga-PSMA-914 PET/CT staging. The procedure was well tolerated without adverse effects.

The dual modality of PSMA-914 has the potential to significantly advance prostate cancer surgery by combining diagnostic imaging and intraoperative guidance. These first results warrant further large-scale clinical trials to validate efficacy and safety across diverse patient populations. The integration of PSMA-914 into clinical protocols promises to benefit prostate cancer surgery by facilitating real-time, high-contrast visualization to aid in complete tumor resection.

Concurrent chemoradiotherapy (cCRT) remains the standard treatment for patients diagnosed with limited-stage small-cell lung cancer (LS-SCLC); however, recurrence rates remain high and prognosis remains poor. This study collected data regarding patient-reported outcomes and adverse events (AEs) to evaluate the effects of chemoradiotherapy combined with immunotherapy in patients with LS-SCLC.

A systematic literature search of 7 electronic databases was conducted for randomized, placebo-controlled trials enrolling patients diagnosed with LS-SCLC who received chemoradiotherapy combined with immunotherapy. Trials with unstratified LS-SCLC samples were excluded. A subsequent meta-analysis was performed. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under accession number CRD42024607159.

Nine trials comprising 1,853 patients were included. CCRT combined with immunotherapy exhibited a significant favorable trend in survival outcomes, with hazard ratios (HRs) for median progression-free survival (mPFS) and median overall survival (mOS) of 0.838 (95% confidence interval [CI]: 0.742-0.947) and 0.847 (95% CI: 0.736-0.975), especially in the consolidation group with HRs for mPFS and mOS of 0.793 (95% CI: 0.675-0.930) and 0.757 (95% CI: 0.551-1.040), respectively.

CCRT combined with immunotherapy improved survival in patients with LS-SCLC, especially in the consolidation immunotherapy group. The treatment regimen was generally well tolerated, with an acceptable incidence of treatment-related adverse events (TRAEs).

https://www.crd.york.ac.uk/prospero/, identifier CRD42024607159.

Cholangiocarcinoma (CCA) is a highly desmoplastic biliary malignancy in which durable benefit from chemotherapy, immune checkpoint blockade, targeted therapy and local treatment remains limited for many patients. Cancer-associated fibroblasts (CAFs) are increasingly recognized as dynamic regulators of immune escape and therapeutic resistance rather than passive matrix-producing bystanders. Here, we propose therapy-imprinted fibroblast memory as a framework for understanding how treatment-conditioned CAF states may persist after therapeutic or tissue-injury pressure and contribute to immune exclusion, residual tumor-cell survival and relapse in CCA. This concept is distinguished from baseline CAF heterogeneity and transient stromal activation by prior therapeutic exposure, persistence beyond the acute injury phase, measurable molecular or spatial signatures, functional effects on tumor or immune behavior, and potential reversibility or targetability. Throughout the review, CCA-specific studies are prioritized to define disease-relevant CAF states, hepatobiliary injury contexts and therapeutic pressures, whereas evidence from pancreatic cancer, breast cancer, colorectal cancer, lung cancer, fibrosis and wound-healing models is used as mechanistic support for conserved stromal biology and hypothesis generation rather than as direct proof of therapy-imprinted CAF memory in CCA. We first summarize the established baseline CAF landscape in treatment-naive CCA, including myofibroblastic, inflammatory, antigen-presentation-like, perivascular and FAP-positive immunoregulatory CAF states. We then discuss how cytotoxic therapy, immune pressure, targeted therapy, radiotherapy, hypoxia, bile-acid stress, cholestasis and wound-healing signals may reshape these baseline programs into persistent post-treatment CAF niches. We further describe how therapy-conditioned CAF programs may reorganize spatial niches at invasive fronts, fibrotic septa, perivascular regions, perineural compartments and immune-excluded tumor borders, thereby supporting residual tumor cells, restricting cytotoxic lymphocyte access and promoting treatment-resistant relapse. Finally, we outline biomarker and therapeutic strategies for identifying and rewiring pathogenic CAF niches using single-cell and spatial multiomics, multiplex imaging, patient-derived models, FAP imaging, senescence-associated interventions, ECM normalization and rational stromal-immunotherapy combinations. This framework emphasizes that post-treatment CAF evolution should be interpreted against the baseline CCA CAF landscape rather than treated as an extension of static CAF taxonomy alone.

Coagulation and inflammation play crucial roles in the initiation and progression of cancer, and they exhibit a synergistic effect. However, a hematological biomarker and risk model based on coagulation and inflammatory have not yet been established in breast cancer.

This study retrospectively analyzed 749 breast cancer patients at our institution. We established a coagulation-inflammation-related genes (CIRGs) risk model using the TCGA-BRCA dataset as the training set and GEO datasets (GSE20685, GSE21653) as the testing sets. Immunohistochemical staining was performed on tumor tissues to validate protein-level expression of key genes. Additionally, single-cell RNA sequencing (scRNA-seq) was applied to investigate the expression of the CIRGs and explore intercellular communication differences.

All enrolled cases were stratified by median systemic coagulation-inflammation index (SCI) into high- and low-SCI groups. The low-SCI group had longer disease-free survival and overall survival than the high-SCI group, with higher SCI levels noted in triple-negative breast cancer (TNBC). SCI exhibited a linear correlation with survival outcomes and superior survival predictive performance compared to the platelet-to-lymphocyte ratio. LASSO regression selected 21 prognosis-related CIRGs to construct a prognostic model, which showed robust predictive efficacy across three datasets. Tumor microenvironment analysis indicated that the high-risk group was associated with immune suppression. Drug sensitivity analysis identified 6 potential candidate drugs for low- and high-risk groups. Four hub genes (ABCA1, IL1R1, SERPINE1, and HPN) were identified among CIRGs, showing strong correlations with tumor stage and prognosis. scRNA-seq analysis revealed high expression of the CIRGs in myeloid, endothelial, and epithelial cells, with higher AUCell scores of the CIRGs in TNBC. Significant intercellular communication differences were observed between the two risk groups, especially in fibroblast/endothelial cell-to-T/B cell signaling pathways.

This study deeply explores the roles and clinical significance of coagulation and inflammation in breast cancer. The hematological indicator SCI and the CIRGs risk model can serve as reliable biomarkers for breast cancer personalized treatment.

Protein O-GlcNAcylation has evolved from a metabolic curiosity into a master post-translational modification that enables cancer cells to translate nutrient availability into coordinated programs of proliferation, therapy resistance, and immune evasion. In this review, we argue that hyper-O-GlcNAcylation is not merely a passive consequence of the Warburg effect but an actively maintained stress-adaptive state that drives malignancy through parallel substrate-selective circuits rather than a single unified axis. We synthesize recent advances in four interconnected dimensions. Metabolically, OGT integrates glucose, lipid, and nucleotide metabolism by modifying key rate-limiting enzymes and is regulated by lineage-specific mechanisms. O-GlcNAcylation modulates responses to chemotherapy and radiotherapy, reinforces DNA damage repair, and controls senescence. Immunologically, it promotes tumor immune evasion by stabilizing PD-L1, reprogramming macrophages, suppressing NK and T cell function, and modulating cGAS-STING signaling, thereby influencing checkpoint blockade efficacy. In the tumor microenvironment, O-GlcNAc signaling remodels the extracellular matrix, drives angiogenesis, and maintains cancer stemness and mechanoadaptation. Collectively, we propose that substrate-selective O-GlcNAc circuits, rather than global OGT activity, are the key drivers of context-dependent malignancy. This framework highlights opportunities for developing next-generation low-toxicity therapeutics, including substrate-selective inhibitors and PROTAC degraders, in rational combinations with chemotherapy, radiotherapy, and immunotherapy.

High-grade gliomas cannot be fully understood without considering the biology of aging. In this study, we demonstrate that a set of genes previously established as predictors of tumor subtype and patient survival in gliomas can also be independently characterized as biomarkers associated with aging. Moreover, their expression changes during aging parallel with those seen in malignant transformation: genes which upregulation worsen prognosis are also upregulated with age. These findings support the hypothesis that glioma progression and aging share partially overlapping molecular mechanisms. We also demonstrate that while accelerated epigenetic and mitotic senescence - gauged by mathematical models (biological clocks) that track aging through specific changes in the DNA methylation of a set of CpG sites - appears inherent to various molecular variants of gliomas, its nature and prognostic significance vary depending on the specific subtype and the epigenetic clock model employed. Moreover, accelerated aging does not represent a universal hallmark of aggressiveness but rather a phenomenon specific to individual glioma subtype. In this paper, we provide a detailed discussion of the role of cellular senescence in glioma pathogenesis, with a particular focus on its key contribution to tumor growth control and therapeutic response. Additionally, we highlight the yet unresolved question of whether age-associated inflammation (inflammaging) acts as an independent driver of glioma progression or whether the tumor itself accelerates aging, and suggest the potential of profiling patients cellular aging in developing personalized treatment strategies.